During the early stages of infections of mice with Fasciola hepatica (6–11 days) the young flukes feed almost exclusively on hepatic cells which the oral sucker and the pharynx have broken down into a kind of homogenate containing Kupffer cells, invading leucocytes and some erythrocytes. As the flukes increase in size liver damage also increases in amount because of the larger burrows which are made. In some instances this does not adversely affect the host but in many infections excessive liver damage produces critical conditions which threaten the life of the host and its parasites. A comparison of the lesions produced in infections lasting 17–25 days with lesions produced after only 6–7 days has shown that the former, unlike the latter, are not due entirely to the feeding activities of the fluke. In short-term infections the inflammatory reaction produces the characteristic effects which are concerned with the healing of fluke tracts, but in older infections this reaction appears to be much more violent and tremendous leucocytic infiltrations break down apparently normal hepatic parenchyma and convert the terminal part of the burrow into a pool containing enormous numbers of invading leucocytes, broken hepatic cells and blood. These are the conditions which prevail at the onset of the critical period, when flukes have their growth inhibited as if by nutritional deficiencies. Some hosts are able to survive the critical period and nurture well-grown flukes for long periods, and may be able to obviate the critical conditions. It is suggested that the excessive damage which occurs in many instances during the critical period is not due to the feeding activities of the larger flukes but is a consequence of less restrained or even unrestrained inflammatory reactions which may lead to more serious pathogenic effects bordering on malignancy. This may be related to differences in the time spent by flukes in the hepatic parenchyma, early entry into the biliary system obviating these effects, late entry facilitating them.